N-[4-o-hydroxyphenyl-1,3-dioxan-5-ylhexenoyl]sulphonamides

Abstract

The invention concerns novel N-[4(Z)-2-substituted-6-(4-o-hydroxyphenyl-1,3 dioxan-cis-5-yl)hexenoyl]sulphonamide derivatives of formula I of value as therapeutic agents. Typically R1 is a branched (3-6C)alkyl, trifluoromethyl or phenyl radical as defined hereinafter and R2 is alkyl, benzyl or phenyl. The invention also discloses salts of the formula I compounds as well as pharmaceutical compositions containing the compounds and processes for the production of the compounds.

What is claimed is: 
     
       1. A sulphonamide derivative of the formula I wherein R 1  is trifluoromethyl, (3-5C) branched alkyl or is phenyl optionally bearing a substituent selected from halogeno, cyano, nitro, trifluoromethyl and (1-4)alkoxy; and R 2  is (1-6C)alkyl, benzyl or phenyl, the latter two of which may optionally bear a substituent selected from halogeno, (1-4C)alkyl, (1-4C)alkoxy, trifluoromethyl, cyano and nitro; and the substituents at positions 4 and 5 of the dioxane ring in formula I and the substituent R 1  have cis-relative stereochemistry; or a pharmaceutically acceptable salt thereof.   
     
     
       2. A compound as claimed in claim 1 wherein R 1  is trifluoromethyl, isopropyl, isobutyl, sec-butyl or t-butyl, or is phenyl optionally bearing a substituent selected from fluoro, chloro, bromo, cyano, nitro, trifluoromethyl, methoxy and ethoxy; and R 2  is methyl, ethyl, propyl, benzyl or phenyl, the latter two optionally bearing a substituent selected from fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, cyano and nitro substituent. 
     
     
       3. A compound as claimed in claim 1 wherein R 1  is isopropyl, t-butyl or trifluoromethyl, or is phenyl optionally bearing a substituent selected from fluoro, chloro, bromo, cyano, nitro, trifluoromethyl and methoxy. 
     
     
       4. A compound as claimed in claim 1 wherein R 1  is isopropyl, t-butyl, trifluoromethyl, 2-chlorophenyl, 2-cyanophenyl, 3-(trifluoromethyl)phenyl, 4-chlorophenyl, 4-cyanophenyl or 4-nitrophenyl. 
     
     
       5. A compound as claimed in claim 1 wherein R 2  is (1-6C)alkyl. 
     
     
       6. A compound selected from the group consisting of N-ethanesulphonyl-4(Z)-6-([2,4,5-cis]-2-o chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-5-yl)hexen amide, N-ethanesulphonyl-4(Z)-6-([2,4,5-cis]-2-p cyanophenyl-4-o-hydroxyphenyl-1,3-dioxan-5-yl)hexen amide, N-methanesulphonyl-4(Z)-6-([2,4,5-cis]-2-t butyl-4-o-hydroxyphenyl-1,3-dioxan-5-yl)hexenamide and the pharmaceutically acceptable salts thereof. 
     
     
       7. A salt as claimed in claims 1 or 6 which is selected from alkali metal, alkaline earth metal, aluminium and ammonium salts, and from salts with organic amines and quaternary bases forming physiologically acceptable cations. 
     
     
       8. A pharmaceutical composition for antagonizing one or more of the actions of thromboxane A 2  which comprises a thromboxane A 2  antagonistically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, as claimed in claim 1 together with a pharmaceutically acceptable diluent or carrier. 
     
     
       9. A composition as claimed in claim 8 which comprises, as an additional active ingredient, an inhibitor of thromboxane A 2  synthesis. 
     
     
       10. A method of antagonising one or more of the actions of thromboxane A 2  in a warm-blooded animal requiring such treatment which comprises administering to said animal an effective amount of a compound of the formula I, or a pharmaceutically acceptable salt thereof, as claimed in claim 1.